1 INDICATIONS AND USAGE

QWO is indicated for the treatment of moderate to severe cellulite in the buttocks of adult women.

6 ADVERSE REACTIONS

The following adverse reactions to QWO for injection are discussed in greater detail in other sections of the labeling:

• Hypersensitivity [see Contraindications (4) and Warnings and Precautions (5.1)].
• Injection Site Bruising [see Warnings and Precautions (5.2)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In two double-blind, placebo-controlled clinical trials (Trials 1 and 2) of identical design, 424 female subjects with cellulite in the buttocks received QWO and 419 female subjects with cellulite received placebo. Enrolled subjects were adults age 18 to 78 years with moderate to severe cellulite (graded as 3 or 4 on a 0 to 4 scale) and without excessive skin laxity. The majority were White (78%) or African American (18%). Subjects completed up to 3 treatment visits separated by 21 days and were followed for up to 6 months after the last treatment visit in a separate open-label extension trial (Trial 3).

Table 3 shows the incidence of adverse reactions that were reported in ≥ 1% of subjects who received QWO-and at a frequency greater than subjects who received placebo in Trials 1 and 2 through Day 71. Generally, adverse reactions had a duration of less than 21 days.

Table 3: Adverse Reactions Occurring in ≥ 1% of Subjects in Trials 1 and 2 Through Day 71

Adverse Reactions at Injection Site	QWO N=424 %	Placebo N=419 %
Bruising	84	21
Pain	48	10
Nodule	33	1
Pruritus	15	1
Erythema	9	5
Discoloration	8	1
Swelling Warmth	8 3	1 0

Pooled terms:

• Bruising - injection site bruising, injection site hematoma, and injection site hemorrhage (refers to verbatim term injection site ecchymosis)
• Pain - injection site pain, injection site discomfort, and injection site dysesthesia
• Swelling - injection site swelling, injection site edema, injection site induration
• Discoloration - injection site discoloration
• Nodule- injection site mass and injection site nodule

Four hundred seventy-nine (479) subjects from Trials 1 and 2 completed a 6-month observation phase in the ongoing open-label safety extension (Trial 3). No long-term safety signals have been identified.

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handing, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other products, including other collagenase clostridium histolyticum products, may be misleading.

By Day 22, approximately 53% (203/383) and 26% (101/383) of subjects who completed the first treatment visit of QWO at the recommended dose in Trials 1 and 2 developed anti-AUX-I and anti-AUX-II antibodies, respectively. The majority (> 96%) of subjects developed antibodies for AUX-I and AUX-II after second and third treatment visits. Antibody titers suggested that antibodies were retained for up to 360 days after receiving the first recommended dose. By Day 71, approximately 68% and 83% of subjects developed antibodies to AUX-I and AUX-II which were classified as neutralizing, respectively.
Antibodies to AUX-I and AUX-II including those classified as neutralizing were not associated with changes in clinical response or adverse reactions at injection site.

6.3 Postmarketing Experience

Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following adverse reaction was reported during post approval use of a collagenase product:

Immune system disorders: serious hypersensitivity reactions including anaphylaxis[see Warnings and Precautions (5.1)].